DESCRIPTION (provided by investigator): The long-term objective of this study is to develop neuroprostheses for persons with spinal cord injury who are unable to voluntarily control their bladder. Our approach is to design an optimal array with penetrating multi-site multi-shank silicon probes for chronic implantation in the sacral spinal cord of intact and spinally transected cats for selective stimulation of neuronal populations involved in micturition reflexes. This approach is based on results of our recently competed NIH contract, where we used an array of discrete microwire electrodes chronically implanted in the S1-S2 spinal cord containing bladder-activating and external urethral sphincter-inhibiting neuronal circuitry. While we were able to induce near-complete bladder emptying in some intact and spinal cord transected cats, the targeting efficiency was insufficient for reliable induction of micturition in every implanted animal. In this proposal, we will utilize advanced silicon microfabrication technology, and particularly the deep-reactive ion etching of silicon wafers, that is more reproducible, scalable, cost-efficient, and clinically-translatable than our current microwire-based fabrication technology. This technology allows placement of multiple electrode sites per shank, full control of probe geometry, and increased flexibility in the array design, all of which would improve our precision and reliability in targeting small populations of neurons in the sacral spinal cord. This research project is design-driven and aims to optimize the silicon probe geometry and density of stimulating sites to achieve reliable neuroprosthetic micturition before as well as after the spinal cord injury. PUBLIC HEALTH RELEVANCE: The long-term objective of this study is to develop neuroprostheses for persons with spinal cord injury who are unable to voluntarily control their bladder. Proposed use of novel technologies in fabricating and in vitro and in vivo testing will allow precise targeting of small populations of neurons in the spinal cord controlling bladder voiding. If this project is successful, it will allow paralyzed animals (and later humans) to control their bladder by intraspinal stimulation, which has better selectivity and fewer side- effects than currently used sacral nerve and root stimulation.